2,026 results match your criteria Pseudohypoparathyroidism

Functional Properties of Two Distinct PTH1R Mutants Associated With Either Skeletal Defects or Pseudohypoparathyroidism.

JBMR Plus 2022 Jun 14;6(6):e10604. Epub 2022 Apr 14.

Endocrine Unit Massachusetts General Hospital, and Harvard Medical School Boston MA USA.

Consistent with a vital role of parathyroid hormone (PTH) receptor type 1 (PTH1R) in skeletal development, homozygous loss-of-function PTH1R mutations in humans results in neonatal lethality (Blomstrand chondrodysplasia), whereas such heterozygous mutations cause a primary failure of tooth eruption (PFE). Despite a key role of PTH1R in calcium and phosphate homeostasis, blood mineral ion levels are not altered in such cases of PFE. Recently, two nonlethal homozygous PTH1R mutations were identified in two unrelated families in which affected members exhibit either dental and skeletal abnormalities (PTH1R-V204E) or hypocalcemia and hyperphosphatemia (PTH1R-R186H). Read More

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Pseudohypoparathyroidism: a diagnosis to consider once a PTH elevation is detected.

Acta Biomed 2022 06 6;93(S3):e2022194. Epub 2022 Jun 6.


Background And Aim: Pseudohypoparathyroidism (PHP) is a rare disease, which can occur in the youth, characterized by hypocalcemia and hyperphosphatemia due to resistance to parathyroid hormone (PTH) in target organs. This condition encompasses different conditions which differ between one another by different clinical, biochemically, and genetic features.

Methods: Herein we report the clinical history of a boy with PHP1B with an interesting clinical presentation. Read More

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Novel genetic variants of KHDC3L and other members of the subcortical maternal complex associated with Beckwith-Wiedemann syndrome or Pseudohypoparathyroidism 1B and multi-locus imprinting disturbances.

Clin Epigenetics 2022 05 28;14(1):71. Epub 2022 May 28.

Department of Environmental Biological and Pharmaceutical Sciences and Technologies (DiSTABiF), Università Degli Studi Della Campania "Luigi Vanvitelli", Caserta, Italy.

Background: Beckwith-Wiedemann syndrome (BWS) and Pseudohypoparathyroidism type 1B (PHP1B) are imprinting disorders (ID) caused by deregulation of the imprinted gene clusters located at 11p15.5 and 20q13.32, respectively. Read More

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Early Diagnosis of Pseudohypoparathyroidism before the Development of Hypocalcemia in a Young Infant.

Children (Basel) 2022 May 15;9(5). Epub 2022 May 15.

Department of Pediatrics, Yeungnam University School of Medicine, Yeungnam University Hospital, Daegu 42415, Korea.

Pseudohypoparathyroidism (PHP) is a rare, heterogeneous disorder characterized by end-organ resistance to parathyroid hormone (PTH). PTH resistance causes elevated PTH levels, hypocalcemia, and hyperphosphatemia. Since hypocalcemia causes life-threatening events, early diagnosis is crucial. Read More

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Fahr syndrome discovered in adulthood revealing a rare mutation in pseudohypoparathyroidism type 1a in a Tunisian family.

Clin Case Rep 2022 May 16;10(5):e05849. Epub 2022 May 16.

Department of Endocrinology Faculty of Medicine of Sousse Ibn Jazzar University Hospital Kairouan University of Medicine Kairouan Tunisia.

Pseudohypoparathyroidism (PHP) indicates a rare heterogeneous group of disorders characterized by hypocalcemia, hyperphosphatemia, increased serum concentration of parathyroid hormone (PTH), and insensitivity to the biologic activity of PTH. One of its most common types is PHP-1a. In this report, we present a familial PHP-1a and a novel mutation of the gene. Read More

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Tertiary hyperparathyroidism in patients with pseudohypoparathyroidism type 1a.

Bone Rep 2022 Jun 14;16:101569. Epub 2022 Apr 14.

Department of Pediatrics, Kanazawa Medical University, Kanazawa, Japan.

Pseudohypoparathyroidism type 1a (PHP1a) is a genetic disorder caused by heterozygous loss-of-function mutations on the maternal allele of the gene. Patients with PHP1a predominantly exhibit parathyroid hormone (PTH) resistance and physical features of Albright's hereditary osteodystrophy. We report two unrelated cases with PHP1a who developed tertiary hyperparathyroidism (HPT). Read More

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Clinical and genetic analysis of pseudohypoparathyroidism complicated by hypokalemia: a case report and review of the literature.

BMC Endocr Disord 2022 Apr 11;22(1):98. Epub 2022 Apr 11.

Department of endocrinology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Pseudohypoparathyroidism (PHP) encompasses a highly heterogenous group of disorders, characterized by parathyroid hormone (PTH) resistance caused by mutations in the GNAS gene or other upstream targets. Here, we investigate the characteristics of a female patient diagnosed with PHP complicated with hypokalemia, and her family members.

Case Presentation And Gene Analysis: A 27-year-old female patient occasionally exhibited asymptomatic hypocalcemia and hypokalemia during her pregnancy 1 year ago. Read More

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Paroxysmal Kinesigenic Dyskinesia Secondary to Pseudohypoparathyroidism Responding to Correction of Calcium.

Mov Disord Clin Pract 2022 Apr 2;9(3):386-389. Epub 2022 Feb 2.

Department of Neurology Indira Gandhi Institute of Medical Sciences Patna India.

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Novel multilocus imprinting disturbances in a child with expressive language delay and intellectual disability.

Am J Med Genet A 2022 Jul 1;188(7):2209-2216. Epub 2022 Apr 1.

Department of Pediatrics, Division of Pediatric Genetics, Metabolism and Genomic Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Multilocus imprinting disturbances (MLID) have been associated with up to 12% of patients with Beckwith-Wiedemann syndrome, Silver-Russell syndrome, and pseudohypoparathyroidism type 1B (PHP1B). Single-gene defects affecting components of the subcortical maternal complex (SCMC) have been reported in cases with multilocus hypomethylation defects. We present a patient with speech and language impairment with mild Angelman syndrome (AS) features who demonstrates maternal hypomethylation at 15q11. Read More

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A novel GNAS variant presents with disorders of GNAS inactivation and cardiomyopathy.

Am J Med Genet A 2022 Jul 29;188(7):2147-2152. Epub 2022 Mar 29.

Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado, Aurora, Colorado, USA.

The GNAS gene (OMIM#139320), located on chromosome 20q13.2, encodes for the alpha-subunit of the stimulatory signaling protein, Gsα protein. GNAS variants with inactivating properties are associated with Albright's hereditary osteodystrophy (AHO) and when maternally inherited, pseudohypoparathyroidism 1a (OMIM#103580), which includes multiple hormone resistance. Read More

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Evaluating the variety of GNAS inactivation disorders and their clinical manifestations in 11 Chinese children.

BMC Endocr Disord 2022 Mar 16;22(1):70. Epub 2022 Mar 16.

Department of Endocrinology and Metabolism, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dongfang Road, Shanghai, 200127, China.

Background: The GNAS gene on chromosome 20q13.3, encodes the alpha-subunit of the stimulatory G protein, which is expressed in most tissues and regulated through reciprocal genomic imprinting. Disorders of GNAS inactivation produce several different clinical phenotypes including pseudohypoparathyroidism (PHP), pseudopseudohypoparathyroidism (PPHP), progressive osseous heteroplasia (POH), and osteoma cutis (OC). Read More

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Intracranial calcifications in pseudohypoparathyroidism type 1b: Report of four cases.

Endocrinol Diabetes Nutr (Engl Ed) 2022 Jan;69(1):70-72

Endocrinology and Nutrition Department, La Paz University Hospital, Madrid, Spain; Department of Medicine, Autonomous University of Madrid (UAM), Madrid, Spain; Endocrine Diseases Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain.

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January 2022

Aberrant Bone Regulation in Albright Hereditary Osteodystrophy dueto Gnas Inactivation: Mechanisms and Translational Implications.

Curr Osteoporos Rep 2022 02 28;20(1):78-89. Epub 2022 Feb 28.

Department of Pediatrics, Division of Pediatric Endocrinology & Diabetes, University of Connecticut School of Medicine, 505 Farmington Ave, 2nd floor, Farmington, CT, 06032, USA.

Purpose Of Review: This review highlights the impact of Gnas inactivation on both bone remodeling and the development of heterotopic subcutaneous ossifications in Albright hereditary osteodystrophy (AHO). Here we discuss recent advancements in understanding the pathophysiologic mechanisms of the aberrant bone development in AHO as well as potential translational implications.

Recent Findings: Gnas inactivation can regulate the differentiation and function of not only osteoblasts but also osteoclasts and osteocytes. Read More

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February 2022

Intralesional sodium thiosulfate treatment of calcinosis cutis in pseudopseudohypoparathyroidism.

Pediatr Dermatol 2022 Feb 25. Epub 2022 Feb 25.

Division of Dermatology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Pseudopseudohypoparathyroidism is an imprinted GNAS spectrum disorder that induces the phenotype of Albright's hereditary osteodystrophy. This phenotype often involves the formation of calcinosis cutis: firm, painful cutaneous eruptions, which are classically difficult to treat. Intralesional sodium thiosulfate has been reported successfully in various cases of calcinosis cutis; however, these reports describe patients with autoimmune or idiopathic calcinosis. Read More

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February 2022

A novel variant in the complex locus causes Albright hereditary osteodystrophy with pseudopseudohypoparathyroidism.

JAAD Case Rep 2022 Mar 19;21:103-105. Epub 2022 Jan 19.

Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts.

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A complex pheotype in a girl with a novel heterozygous missense variant (p.Ile56Phe) of the GNAS gene.

Orphanet J Rare Dis 2022 02 23;17(1):83. Epub 2022 Feb 23.

Pediatric Division, Department of Pediatrics, University Hospital of Verona, Piazzale Stefani 1, 37126, Verona, Italy.

Background: GNAS is a complex gene that encodes Gsα, a signaling protein that triggers a complex network of pathways. Heterozygous inactivating mutations in Gsα-coding GNAS exons cause hormonal resistance; on the contrary, activating mutations in Gsα result in constitutive cAMP stimulation. Recent research has described a clinical condition characterized by both gain and loss of Gsα function, due to a heterozygous de novo variant of the maternal GNAS allele. Read More

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February 2022

Novel PTH Gene Mutations Causing Isolated Hypoparathyroidism.

J Clin Endocrinol Metab 2022 05;107(6):e2449-e2458

Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA.

Context: Parathyroid hormone (PTH) gene mutations represent a rare cause of familial isolated hypoparathyroidism (FIH). These defects can cause hypoparathyroidism with increased or decreased serum levels of PTH through 1) impaired PTH synthesis; 2) induction of parathyroid cell apoptosis; or 3) secretion of bioinactive PTH molecules. Eight pathogenic mutations of this gene have been described previously. Read More

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Pseudohypoparathyroidism type 1 B mimicking Fahr's disease in a 28-year-old female: A case report.

Clin Case Rep 2022 Feb 6;10(2):e05418. Epub 2022 Feb 6.

Department of Internal Medicine, Maharajgunj Medical Campus Tribhuvan University Institute of Medicine Kathmandu Nepal.

In virtue of precise clinical history, physical examinations, and biochemical/radiological investigations, pseudohypoparathyroidism can be effectively diagnosed, and its types can be differentiated even without exorbitant tests. Read More

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February 2022

Autosomal dominant pseudohypoparathyroidism type 1B due to STX16 deletion: a case presentation and literature review.

Minerva Endocrinol (Torino) 2022 Feb 4. Epub 2022 Feb 4.

Department of Endocrinology, .424 General Military Hospital, Thessaloniki, Greece.

Introduction: Pseudohypoparathyroidism (PHP) is a heterogeneous group of rare, genetically related, endocrine disorders, characterized by end-organ resistance to parathyroid hormone (PTH) action and other G protein-coupled receptors (GPCRs) related hormones. The clinical variants of PHP are classified according to the presence of features of Albright's Hereditary Osteodystrophy (AHO) and in vivo response to exogenous PTH. Autosomal dominant PHP1b is often caused by a deletion in the Syntaxin-16 (STX16) gene, leading to a loss of methylation in the A/B exon of the guanine nucleotide-binding protein a-stimulating polypeptide (GNAS) complex. Read More

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February 2022

A novel deletion involving the first GNAS exon encoding Gsα causes PHP1A without methylation changes at exon A/B.

Bone 2022 04 29;157:116344. Epub 2022 Jan 29.

Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Pediatric Nephrology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:

Individuals affected by pseudohypoparathyroidism type 1A (PHP1A) display hyperphosphatemia and hypocalcemia despite elevated PTH levels, as well as features of Albright Hereditary Osteodystrophy (AHO). PHP1A is caused by variants involving the maternal GNAS exons 1-13 encoding the stimulatory G protein α-subunit (Gsα). MLPA and aCGH analysis led in a male PHP1A patient to identification of a de novo 1284-bp deletion involving GNAS exon 1. Read More

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Parental Origin of Inactivation Differentially Affects Bone Remodeling in a Mouse Model of Albright Hereditary Osteodystrophy.

JBMR Plus 2022 Jan 16;6(1):e10570. Epub 2021 Nov 16.

Department of Pediatrics University of Connecticut School of Medicine Farmington CT USA.

Albright hereditary osteodystrophy (AHO) is caused by heterozygous inactivation of , a complex locus that encodes the alpha-stimulatory subunit of heterotrimeric G proteins (Gsα) in addition to and α due to alternative first exons. AHO skeletal manifestations include brachydactyly, brachymetacarpia, compromised adult stature, and subcutaneous ossifications. AHO patients with maternally-inherited mutations develop pseudohypoparathyroidism type 1A (PHP1A) with resistance to multiple hormones that mediate their actions through G protein-coupled receptors (GPCRs) requiring Gsα (eg, parathyroid hormone [PTH], thyroid-stimulating hormone [TSH], growth hormone-releasing hormone [GHRH], calcitonin) and severe obesity. Read More

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January 2022

Genetics of monogenic disorders of calcium and bone metabolism.

Clin Endocrinol (Oxf) 2021 Dec 21. Epub 2021 Dec 21.

Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology & Metabolism (OCDEM), Churchill Hospital, University of Oxford, Oxford, UK.

Disorders of calcium homeostasis are the most frequent metabolic bone and mineral disease encountered by endocrinologists. These disorders usually manifest as primary hyperparathyroidism (PHPT) or hypoparathyroidism (HP), which have a monogenic aetiology in 5%-10% of cases, and may occur as an isolated endocrinopathy, or as part of a complex syndrome. The recognition and diagnosis of these disorders is important to facilitate the most appropriate management of the patient, with regard to both the calcium-related phenotype and any associated clinical features, and also to allow the identification of other family members who may be at risk of disease. Read More

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December 2021

Novel Pathogenetic Variants in PTHLH and TRPS1 Genes Causing Syndromic Brachydactyly.

J Bone Miner Res 2022 03 17;37(3):465-474. Epub 2022 Jan 17.

Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Skeletal disorders, including both isolated and syndromic brachydactyly type E, derive from genetic defects affecting the fine tuning of the network of pathways involved in skeletogenesis and growth-plate development. Alterations of different genes of this network may result in overlapping phenotypes, as exemplified by disorders due to the impairment of the parathyroid hormone/parathyroid hormone-related protein pathway, and obtaining a correct diagnosis is sometimes challenging without a genetic confirmation. Five patients with Albright's hereditary osteodystrophy (AHO)-like skeletal malformations without a clear clinical diagnosis were analyzed by whole-exome sequencing (WES) and novel potentially pathogenic variants in parathyroid hormone like hormone (PTHLH) (BDE with short stature [BDE2]) and TRPS1 (tricho-rhino-phalangeal syndrome [TRPS]) were discovered. Read More

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Lack of GNAS Remethylation During Oogenesis May Be a Cause of Sporadic Pseudohypoparathyroidism Type Ib.

J Clin Endocrinol Metab 2022 03;107(4):e1610-e1619

Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Context: Pseudohypoparathyroidism type Ib (PHP1B) is characterized by hypocalcemia and hyperphosphatemia due to parathyroid hormone resistance in the proximal renal tubules. Maternal pathogenic STX16/GNAS variants leading to maternal epigenetic GNAS changes impair expression of the stimulatory G protein alpha-subunit (Gsα) thereby causing autosomal dominant PHP1B. In contrast, genetic defects responsible for sporadic PHP1B (sporPHP1B) remain mostly unknown. Read More

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Parathyroid Hormone Resistance and Autoantibodies to the PTH1 Receptor.

N Engl J Med 2021 11;385(21):1974-1980

From the Metabolic Diseases Branch (A.M., J.W., W.F.S., S.K.A., J.E.B., L.S.W.) and the Kidney Diseases Branch (M.A.W., J.E.B.), National Institute of Diabetes and Digestive and Kidney Diseases, the Adeno-Associated Virus Biology Section (P.D.B., G.D.P., J.A.C.), Salivary Disorders Unit (B.M.W.), and Skeletal Disorders and Mineral Homeostasis Section (M.T.C.), National Institute of Dental and Craniofacial Research, the Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (M.S.L.), the Symptom Management Branch, National Institute of Nursing Research (B.W.), and the Department of Laboratory Medicine, Clinical Center (S.D.R.), National Institutes of Health, Bethesda, MD; and Kaiser Permanente, Sacramento, CA (Y.S.T.).

We describe two cases of acquired parathyroid hormone (PTH) resistance consequent to the development of serum PTH type 1 receptor (PTH1R) autoantibodies, which block PTH binding and signaling. Both cases were associated with other autoimmune manifestations, and one case was associated with atypical membranous glomerulonephritis. In vitro binding and signaling assays identified the presence of PTH1R-blocking IgG autoantibodies, which were not present in serum samples from patients with other renal or autoimmune disorders. Read More

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November 2021

Calcitriol and Levothyroxine Dosing for Patients With Pseudohypoparathyroidism.

J Endocr Soc 2021 Dec 27;5(12):bvab161. Epub 2021 Oct 27.

Division of Pediatric Endocrinology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.

Pseudohypoparathyroidism (PHP) is a rare hormone resistance syndrome caused by mutations in . This cross-sectional study investigated whether PHP patients with parathyroid hormone (PTH), thyrotropin (thyroid stimulating hormone; TSH), and free thyroxine (T4) levels at goal required higher doses of levothyroxine and calcitriol than recommended by current guidelines to overcome mineral ion abnormalities due to hormone resistance. Baseline demographic and clinical data of participants enrolled in PHP research studies between 2012-2021 were collected via retrospective chart review. Read More

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December 2021

Sporadic Pseudohypoparathyroidism Type 1B in Monozygotic Twins: Insights Into the Pathogenesis of Methylation Defects.

J Clin Endocrinol Metab 2022 02;107(3):e947-e954

Department of Diabetes and Endocrinology, Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan.

Context: Sporadic pseudohypoparathyroidism type 1B (sporPHP1B) is an imprinting disease without a defined genetic cause, characterized by broad methylation changes in differentially methylated regions (DMRs) of the GNAS gene.

Objective: This work aims to provide insights into the causative event leading to the GNAS methylation defects through comprehensive molecular genetic analyses of a pair of female monozygotic twins concordant for sporPHP1B who were conceived naturally, that is, without assisted reproductive techniques.

Methods: Using the leukocyte genome of the twins and family members, we performed targeted bisulfite sequencing, methylation-sensitive restriction enzyme (MSRE)-quantitative polymerase chain reaction (qPCR), whole-genome sequencing (WGS), high-density single-nucleotide polymorphism (SNP) array, and Sanger sequencing. Read More

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February 2022

Molecular genetic analysis and growth hormone response in patients with syndromic short stature.

BMC Med Genomics 2021 11 5;14(1):261. Epub 2021 Nov 5.

Department of Paediatrics, Beijing Jishuitan Hospital, No. 31 of Xinjiekou Dongjie Street, Xi Cheng District, Beijing, 100035, People's Republic of China.

Background: Syndromic short stature is a genetic and phenotypic heterogeneous disorder with multiple causes. This study aims to identify genetic causes in patients with syndromic short stature of unknown cause and evaluate the efficacy of the growth hormone response.

Methods: Trio-whole-exome sequencing was applied to identify pathogenic gene mutations in seven patents with short stature, multiple malformations, and/or intellectual disability. Read More

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November 2021

A unique case of bilateral triceps avulsion fracture in a patient with pseudohypoparathyroidism.

Shoulder Elbow 2021 Jun 25;13(3):334-338. Epub 2019 Sep 25.

Trauma & Orthopaedic Department, Royal Free Hospital NHS Trust, Barnet Hospital, Barnet, UK.

Triceps tendon ruptures and avulsions are rare injuries and are often associated with systemic diseases. This paper illustrates the unique case of a 20-year-old female patient with pseudohypoparathyroidism, who sustained bilateral triceps avulsion fractures after a fall. She underwent suture anchor fixation, augmented with tension band suture as double row repair with excellent post-operative results. Read More

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